James H. Tabibian

Complications, symptoms, quality of life and pregnancy in cholestatic liver disease

Cholestatic liver diseases (CLDs) encompass a variety of disorders of bile formation and/or flow which generally result in progressive hepatobiliary injury and ultimately end‐stage liver disease. Many patients with CLD are diagnosed between the ages of 20‐50 years, a particularly productive period of life professionally, biologically and in other respects; it is not surprising, thus, that CLD is often associated with impaired health‐related quality of life (HRQOL) and uncertainty regarding implications for and outcomes of pregnancy. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are the most prominent CLDs, both having considerable morbidity and mortality and representing major indications for liver transplantation. These disorders, as a consequence of their complications (eg ascites, hepatic osteodystrophy), associated conditions (eg inflammatory bowel disease) and symptoms (eg pruritus and fatigue), can significantly impair an array of domains of HRQOL. Here we review these impactful clinical aspects of PSC and PBC as well as the topics of fertility and pregnancy.

Hemobilia: Perspective and Role of the Advanced Endoscopist

Hemobilia refers to bleeding from and/or into the biliary tract and is an uncommon cause of gastrointestinal hemorrhage. Hemobilia has been documented since the 1600s, but due to its relative rarity, it has only been more critically examined in recent decades. Most cases of hemobilia are iatrogenic and caused by procedures involving the liver, pancreas, bile ducts, and/or the hepatopancreatobiliary vasculature, with trauma and malignancy representing the two other major causes. A classic triad of right upper quadrant pain, jaundice, and overt upper gastrointestinal bleeding has been described, but this is present in only 25–30% of patients with hemobilia. Historically, the gold standard for diagnosis and treatment has been angiography and interventional radiologic intervention, respectively. However, the paradigm is shifting, at least in select cases, towards first-line reliance on noninvasive imaging (e.g., computed tomography) and therapeutic endoscopy, owing to advances in and the less invasive nature of both, while saving interventional radiological and/or surgical intervention for refractory or imminently life-threatening cases.

Emerging therapeutic targets for primary sclerosing cholangitis

ABSTRACT Introduction: Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease that can progress to end-stage cirrhotic liver disease and/or hepatobiliary malignancy. The etiopathogenesis of PSC remains unknown, and considerable heterogeneity is seen both phenotypically as well as genetically; this, together with its relative rarity and the lack of consensus regarding appropriate (surrogate) clinical endpoints, has hampered the development and implementation of effective pharmacologic therapies. Several different disease mechanisms have been proposed which have led to various potential therapeutic approaches. However, to date, no medical therapies short of liver transplantation have been proven to be effective for PSC, and as such, liver transplantation – an option for only a fraction of patients – remains the only potentially curative therapy. Areas covered: This review will highlight the various different proposed mechanisms of the etiopathogenesis of PSC and explore the therapeutic targets corresponding to them which are anticipated to be or are already under clinical investigation. Expert commentary: The development of new therapies for PSC remains challenging due to numerous factors, not the least of which are the rare and pathobiologically enigmatic nature of the disease. However, with recent advances in the understanding of potential mechanistic underpinnings and lateral insights from other liver diseases, new potential targets and novel therapeutic agents are being evaluated; we believe these have the potential to lead to the establishment of safe and effective medical therapies and thus better outcomes in PSC.

Endoscopic management of primary sclerosing cholangitis

ABSTRACT Introduction: Primary sclerosing cholangitis (PSC) is a rare but clinically important cholestatic liver disease. Histopathologically and cholangiographically, PSC is characterized by intra- and/or extra-hepatic bile duct inflammation and fibro-obliteration, which ultimately leads to biliary cirrhosis and related sequelae, including development of hepatobiliary and colorectal carcinomata. PSC can be diagnosed at essentially any age and carries a median survival of 15–20 years, regardless of age at diagnosis, and is a foremost risk factor for cholangiocarcinoma. Given the chronic and progressive nature of PSC, its inherent association with both neoplastic and non-neoplastic biliary tract complications, and the lack of effective pharmacotherapies, alimentary and biliary tract endoscopy plays a major role in the care of patients with PSC. Areas covered: Here, we provide a narrative review on endoscopic management of PSC, including established and evolving applications to the diagnosis and treatment of both its benign and malignant complications. Expert commentary: Due to the rarity of PSC and the considerable patient-years required to rigorously study major endpoints, there remains a paucity of high-quality evidence regarding its management. As the advanced endoscopic repertoire expands, so has the interest in developing best practices in PSC, which we discuss herein.

Training in ERCP: a multifaceted enterprise now more than ever

Dear Editor: We read with great interest the recent article by Frost et al. examining whether trainee involvement in endoscopic retrograde cholangiopancreatography (ERCP) is detrimental to cannulation success [1]. ERCP training has evolved considerably over the last 15 years, and the definition of competency in ERCP has expanded well beyond the ability to cannulate a duct of interest to incorporate clinical decision-making and imaging interpretation. Contemporaneously, clinical demands (e. g. decreases in diagnostic ERCP case volume, need to minimize procedural duration, increasing concerns regarding safety, and relative value unitbased compensation models) have continued to place ERCP training at a premium [2]. Therefore, the study by Frost et al. is timely and relevant. The study prospectively followed 2 senior consultant endoscopists and their 3 trainees (all with < 50 prior ERCP experience) over an 18-month period in a United Kingdom hospital with a caseload of approximately 330 ERCPs/year. Presence of a trainee was not randomized but rather “pragmatic,” and only native papillae were included. Once the duodenal papilla (major or minor, depending on the particular) was reached and stable scope position attained, 6 minutes were allotted for cannulation; if achieved, the trainee was allowed to continue, otherwise the supervising consultant would resume. A total of 219 ERCPs were analyzed (134 with trainee, 85 without); procedure difficulty was 61% grade 1, 37% grade 2, and 2% grade 3 [3]. The central findings were that: 1) cannulation success was similar with or without a trainee present (91% vs. 93%, P=0.8); and 2) mean time to biliary cannulation with a trainee present was 7 minutes, compared to 5 minutes without trainee. No serious adverse events were reported. The investigators’ main conclusion was that with their ERCP training protocol, trainee involvement in routine secondary care ERCP does not decrease cannulation success. The study and its aims are commendable; however, several questions should be considered when interpreting the findings and potentially applying them broadly: 1) Were the two groups balanced (e. g. with regard to patient age, gender, and location and appearance of the papilla); 2) Could “pragmatic” determination of trainee participation have led to triaging of complex or challenging cases to consultant only; 3) Is the 6-minute rule used in the training protocol irrespective of number of “touches” or patient-level (e. g. anatomical) factors? Previous research has found that 10 minutes may be most appropriate for trainees to attempt cannulation [4], thus the basis for the 6-minute interval is curious; 4) At what number of ERCPs, on average, did the trainees in the investigators’ training protocol achieve competency; and 5) There were no cases of “complicated pancreatitis” out of the 219 ERCPs included in the study; did any patients require hospitalization or additional investigation for pancreatitis (but no “further intervention” per se)? Having no cases of post-ERCP pancreatitis out of 219 ERCPs represents a markedly low incidence. Answers to the aforementioned questions could greatly enhance interpretation and generalizability of the study findings. In addition, propensity scorebased sensitivity analysis or other statistical methods (e. g. multivariate logistic regression) could be implemented to help strengthen the study and its findings [5]. Ultimately, a larger, well-designed randomized trial would best evaluate the impact of trainee involvement and delineate optimal ERCP training protocols.